JP2018502889A - イソエルゴリン化合物およびその使用 - Google Patents
イソエルゴリン化合物およびその使用 Download PDFInfo
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- JP2018502889A JP2018502889A JP2017538942A JP2017538942A JP2018502889A JP 2018502889 A JP2018502889 A JP 2018502889A JP 2017538942 A JP2017538942 A JP 2017538942A JP 2017538942 A JP2017538942 A JP 2017538942A JP 2018502889 A JP2018502889 A JP 2018502889A
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- alkyl
- substituted
- arylalkyl
- hydrogen
- heteroalkyl
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- 235000019260 propionic acid Nutrition 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 229940100618 rectal suppository Drugs 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 230000021148 sequestering of metal ion Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- DCQXTYAFFMSNNH-UHFFFAOYSA-M sodium;2-[bis(2-hydroxyethyl)amino]ethanol;acetate Chemical compound [Na+].CC([O-])=O.OCCN(CCO)CCO DCQXTYAFFMSNNH-UHFFFAOYSA-M 0.000 description 1
- 239000008137 solubility enhancer Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 229940084106 spermaceti Drugs 0.000 description 1
- 239000012177 spermaceti Substances 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 description 1
- 229960003708 sumatriptan Drugs 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- ZUHZGEOKBKGPSW-UHFFFAOYSA-N tetraglyme Chemical compound COCCOCCOCCOCCOC ZUHZGEOKBKGPSW-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 235000019303 thiodipropionic acid Nutrition 0.000 description 1
- 229940098465 tincture Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- YFNKIDBQEZZDLK-UHFFFAOYSA-N triglyme Chemical compound COCCOCCOCCOC YFNKIDBQEZZDLK-UHFFFAOYSA-N 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000008136 water-miscible vehicle Substances 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C07D457/10—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid with hetero atoms directly attached in position 8
- C07D457/12—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/06—Peri-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/06—Peri-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US201562105207P | 2015-01-20 | 2015-01-20 | |
US62/105,207 | 2015-01-20 | ||
PCT/US2016/013978 WO2016118539A2 (en) | 2015-01-20 | 2016-01-20 | Isoergoline compounds and uses thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2018502889A true JP2018502889A (ja) | 2018-02-01 |
Family
ID=56407316
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017538942A Pending JP2018502889A (ja) | 2015-01-20 | 2016-01-20 | イソエルゴリン化合物およびその使用 |
Country Status (10)
Country | Link |
---|---|
US (3) | US9676776B2 (he) |
EP (1) | EP3247357A4 (he) |
JP (1) | JP2018502889A (he) |
CN (1) | CN107405346A (he) |
AU (1) | AU2016209490B2 (he) |
BR (1) | BR112017015510A2 (he) |
CA (1) | CA2974113A1 (he) |
IL (1) | IL253459B (he) |
MX (1) | MX2017009406A (he) |
WO (1) | WO2016118539A2 (he) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2018502889A (ja) | 2015-01-20 | 2018-02-01 | エックスオーシー ファーマシューティカルズ インコーポレイテッドXoc Pharmaceuticals, Inc | イソエルゴリン化合物およびその使用 |
CN107428745A (zh) | 2015-01-20 | 2017-12-01 | Xoc制药股份有限公司 | 麦角灵化合物及其用途 |
WO2018223065A1 (en) | 2017-06-01 | 2018-12-06 | Xoc Pharmaceuticals, Inc. | Ergoline derivatives for use in medicine |
Family Cites Families (137)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA470573A (en) | 1951-01-02 | Stoll Arthur | Sympatheticolytically active dihydro-derivatives of lysergic acid amides and their manufacture | |
US2086559A (en) | 1936-01-30 | 1937-07-13 | Lilly Co Eli | Hydrogenated ergotocin |
GB1227006A (he) | 1967-04-20 | 1971-03-31 | ||
US3536809A (en) | 1969-02-17 | 1970-10-27 | Alza Corp | Medication method |
US3598123A (en) | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
SE396753B (sv) | 1970-05-18 | 1977-10-03 | Richter Gedeon Vegyeszet | Analogiforfarande for framstellning av en forening tillhorande dihydrolysergsyraserien |
US3710795A (en) | 1970-09-29 | 1973-01-16 | Alza Corp | Drug-delivery device with stretched, rate-controlling membrane |
US4044126A (en) | 1972-04-20 | 1977-08-23 | Allen & Hanburys Limited | Steroidal aerosol compositions and process for the preparation thereof |
GB1429184A (en) | 1972-04-20 | 1976-03-24 | Allen & Hanburys Ltd | Physically anti-inflammatory steroids for use in aerosols |
US3845770A (en) | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
USRE28819E (en) | 1972-12-08 | 1976-05-18 | Syntex (U.S.A.) Inc. | Dialkylated glycol compositions and medicament preparations containing same |
US3916899A (en) | 1973-04-25 | 1975-11-04 | Alza Corp | Osmotic dispensing device with maximum and minimum sizes for the passageway |
US3922347A (en) | 1974-12-19 | 1975-11-25 | Lilly Co Eli | Method of inhibiting prolactin secretion with 8-acylaminoergolenes |
US4008719A (en) | 1976-02-02 | 1977-02-22 | Alza Corporation | Osmotic system having laminar arrangement for programming delivery of active agent |
CH644606A5 (de) * | 1980-09-23 | 1984-08-15 | Sandoz Ag | Verfahren zur isomerisierung von 9,10-dihydrolysergsaeurederivaten. |
US4410545A (en) | 1981-02-13 | 1983-10-18 | Syntex (U.S.A.) Inc. | Carbonate diester solutions of PGE-type compounds |
US4328245A (en) | 1981-02-13 | 1982-05-04 | Syntex (U.S.A.) Inc. | Carbonate diester solutions of PGE-type compounds |
US4358603A (en) | 1981-04-16 | 1982-11-09 | Syntex (U.S.A.) Inc. | Acetal stabilized prostaglandin compositions |
FI76085C (fi) | 1981-07-21 | 1988-09-09 | Erba Farmitalia | Foerfarande foer framstaellning av ergolinderivat. |
DE3135305C2 (de) | 1981-09-03 | 1983-07-21 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Verfahren zur Herstellung von 8-Ergolinyl-harnstoffen |
US4409239A (en) | 1982-01-21 | 1983-10-11 | Syntex (U.S.A.) Inc. | Propylene glycol diester solutions of PGE-type compounds |
CS231214B1 (en) | 1982-03-12 | 1984-10-15 | Antonin Cerny | Processing method of 1-substituted n+l8alpha-ergoline+p-n,diethyl urea |
US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
DE3340025C2 (de) * | 1983-11-03 | 1986-01-09 | Schering AG, 1000 Berlin und 4709 Bergkamen | Verfahren zur Herstellung von 2-Brom-8-ergolinyl-Verbindungen |
NL193541C (nl) * | 1984-01-12 | 2000-01-04 | Novartis Ag | 8 Alfa-acylaminoergolinen, werkwijzen voor de bereiding daarvan en preparaten die ze bevatten. |
DE3413660A1 (de) * | 1984-04-09 | 1985-10-17 | Schering AG, 1000 Berlin und 4709 Bergkamen | Verfahren zur herstellung von 2-(trialkyl-silyl)-ergolinderivaten |
DE3413657A1 (de) * | 1984-04-09 | 1985-10-17 | Schering AG, 1000 Berlin und 4709 Bergkamen | Neue ergoline |
KR890002631B1 (ko) | 1984-10-04 | 1989-07-21 | 몬산토 캄파니 | 생물학적으로 활성인 소마토트로핀을 지속적으로 유리하는 조성물 |
IE58110B1 (en) | 1984-10-30 | 1993-07-14 | Elan Corp Plc | Controlled release powder and process for its preparation |
US4679462A (en) | 1984-12-24 | 1987-07-14 | Sundstrand Corporation | Differential transmission mechanism for a constant speed drive |
EP0208417A3 (en) | 1985-06-12 | 1989-09-06 | SPOFA Spojené Podniky Pro Zdravotnickou Vyrobu | Use of 1-(8-alpha-ergolinyl)-3,3-diethyl urea derivatives in the treatment of endometritis |
HUT45248A (en) * | 1986-01-24 | 1988-06-28 | Sandoz Ag | Process for producing 8alpha-(acylamino)-ergoline derivatives and pharmaceuticals comprising such compounds |
DE3623503A1 (de) * | 1986-07-09 | 1988-01-21 | Schering Ag | 1-aryl-ergolinyl-harnstoffderivate, verfahren zu deren herstellung sowie die verwendung dieser verbindungen als arzneimittel |
US5033252A (en) | 1987-12-23 | 1991-07-23 | Entravision, Inc. | Method of packaging and sterilizing a pharmaceutical product |
US5052558A (en) | 1987-12-23 | 1991-10-01 | Entravision, Inc. | Packaged pharmaceutical product |
US4828950A (en) | 1987-12-28 | 1989-05-09 | Eastman Kodak Company | Method for making multi-color reproductions on plain bond paper |
US5668155A (en) | 1988-05-10 | 1997-09-16 | The General Hospital Corporation | Administration of pirenzepine, methyl scopolamine and other muscarinic receptor antagonists for treatment of lipid metabolism disorders |
US5073543A (en) | 1988-07-21 | 1991-12-17 | G. D. Searle & Co. | Controlled release formulations of trophic factors in ganglioside-lipsome vehicle |
IT1229203B (it) | 1989-03-22 | 1991-07-25 | Bioresearch Spa | Impiego di acido 5 metiltetraidrofolico, di acido 5 formiltetraidrofolico e dei loro sali farmaceuticamente accettabili per la preparazione di composizioni farmaceutiche in forma a rilascio controllato attive nella terapia dei disturbi mentali organici e composizioni farmaceutiche relative. |
DE3915950A1 (de) * | 1989-05-12 | 1990-11-15 | Schering Ag | 8(alpha)-acylamino-ergoline, ihre herstellung und verwendung als arzneimittel |
PH30995A (en) | 1989-07-07 | 1997-12-23 | Novartis Inc | Sustained release formulations of water soluble peptides. |
DE3931819A1 (de) | 1989-09-20 | 1991-03-28 | Schering Ag | 13-brom und 13, 14-dibrom-ergoline, ihre herstellung und verwendung in arzneimitteln |
US5120548A (en) | 1989-11-07 | 1992-06-09 | Merck & Co., Inc. | Swelling modulated polymeric drug delivery device |
US5585112A (en) | 1989-12-22 | 1996-12-17 | Imarx Pharmaceutical Corp. | Method of preparing gas and gaseous precursor-filled microspheres |
IT1246382B (it) | 1990-04-17 | 1994-11-18 | Eurand Int | Metodo per la cessione mirata e controllata di farmaci nell'intestino e particolarmente nel colon |
US5733566A (en) | 1990-05-15 | 1998-03-31 | Alkermes Controlled Therapeutics Inc. Ii | Controlled release of antiparasitic agents in animals |
US5543390A (en) | 1990-11-01 | 1996-08-06 | State Of Oregon, Acting By And Through The Oregon State Board Of Higher Education, Acting For And On Behalf Of The Oregon Health Sciences University | Covalent microparticle-drug conjugates for biological targeting |
DE4123587A1 (de) | 1991-07-12 | 1993-01-14 | Schering Ag | 2,14-disubstituierte ergoline, deren herstellung und verwendung in arzneimitteln |
US5580578A (en) | 1992-01-27 | 1996-12-03 | Euro-Celtique, S.A. | Controlled release formulations coated with aqueous dispersions of acrylic polymers |
US6010715A (en) | 1992-04-01 | 2000-01-04 | Bertek, Inc. | Transdermal patch incorporating a polymer film incorporated with an active agent |
US6024975A (en) | 1992-04-08 | 2000-02-15 | Americare International Diagnostics, Inc. | Method of transdermally administering high molecular weight drugs with a polymer skin enhancer |
US5323907A (en) | 1992-06-23 | 1994-06-28 | Multi-Comp, Inc. | Child resistant package assembly for dispensing pharmaceutical medications |
TW333456B (en) | 1992-12-07 | 1998-06-11 | Takeda Pharm Ind Co Ltd | A pharmaceutical composition of sustained-release preparation the invention relates to a pharmaceutical composition of sustained-release preparation which comprises a physiologically active peptide. |
US5591767A (en) | 1993-01-25 | 1997-01-07 | Pharmetrix Corporation | Liquid reservoir transdermal patch for the administration of ketorolac |
US6274552B1 (en) | 1993-03-18 | 2001-08-14 | Cytimmune Sciences, Inc. | Composition and method for delivery of biologically-active factors |
US5985307A (en) | 1993-04-14 | 1999-11-16 | Emory University | Device and method for non-occlusive localized drug delivery |
US5523092A (en) | 1993-04-14 | 1996-06-04 | Emory University | Device for local drug delivery and methods for using the same |
US6087324A (en) | 1993-06-24 | 2000-07-11 | Takeda Chemical Industries, Ltd. | Sustained-release preparation |
US6004534A (en) | 1993-07-23 | 1999-12-21 | Massachusetts Institute Of Technology | Targeted polymerized liposomes for improved drug delivery |
IT1270594B (it) | 1994-07-07 | 1997-05-07 | Recordati Chem Pharm | Composizione farmaceutica a rilascio controllato di moguisteina in sospensione liquida |
US5759542A (en) | 1994-08-05 | 1998-06-02 | New England Deaconess Hospital Corporation | Compositions and methods for the delivery of drugs by platelets for the treatment of cardiovascular and other diseases |
US5660854A (en) | 1994-11-28 | 1997-08-26 | Haynes; Duncan H | Drug releasing surgical implant or dressing material |
US5983134A (en) | 1995-04-23 | 1999-11-09 | Electromagnetic Bracing Systems Inc. | Electrophoretic cuff apparatus drug delivery system |
US6316652B1 (en) | 1995-06-06 | 2001-11-13 | Kosta Steliou | Drug mitochondrial targeting agents |
CA2224381A1 (en) | 1995-06-27 | 1997-01-16 | Takeda Chemical Industries, Ltd. | Method of producing sustained-release preparation |
EP0882384A4 (en) | 1995-07-14 | 1999-03-24 | Olin Corp | WELDED GRID ELECTRONIC BOX |
US6167301A (en) | 1995-08-29 | 2000-12-26 | Flower; Ronald J. | Iontophoretic drug delivery device having high-efficiency DC-to-DC energy conversion circuit |
TW448055B (en) | 1995-09-04 | 2001-08-01 | Takeda Chemical Industries Ltd | Method of production of sustained-release preparation |
JP2909418B2 (ja) | 1995-09-18 | 1999-06-23 | 株式会社資生堂 | 薬物の遅延放出型マイクロスフイア |
US6039975A (en) | 1995-10-17 | 2000-03-21 | Hoffman-La Roche Inc. | Colon targeted delivery system |
US5980945A (en) | 1996-01-16 | 1999-11-09 | Societe De Conseils De Recherches Et D'applications Scientifique S.A. | Sustained release drug formulations |
US20010016582A1 (en) | 1997-04-28 | 2001-08-23 | Anthony H. Cincotta | Method and composition for the treatment of lipid and glucose metabolism disorders |
CA2257084A1 (en) | 1996-06-06 | 1997-12-11 | Anthony H. Cincotta | Treatment of lipid and glucose metabolism disorders with dopamine and serotonin agonists |
US5877183A (en) | 1996-06-06 | 1999-03-02 | Ergo Research Corporation | Treatment of lipid and glucose metabolism disorders with dopamine and serotonin agonists |
US6264970B1 (en) | 1996-06-26 | 2001-07-24 | Takeda Chemical Industries, Ltd. | Sustained-release preparation |
US6419961B1 (en) | 1996-08-29 | 2002-07-16 | Takeda Chemical Industries, Ltd. | Sustained release microcapsules of a bioactive substance and a biodegradable polymer |
US5985317A (en) | 1996-09-06 | 1999-11-16 | Theratech, Inc. | Pressure sensitive adhesive matrix patches for transdermal delivery of salts of pharmaceutical agents |
US6139865A (en) | 1996-10-01 | 2000-10-31 | Eurand America, Inc. | Taste-masked microcapsule compositions and methods of manufacture |
CA2217134A1 (en) | 1996-10-09 | 1998-04-09 | Sumitomo Pharmaceuticals Co., Ltd. | Sustained release formulation |
US6221070B1 (en) | 1996-10-18 | 2001-04-24 | Irvine Biomedical, Inc. | Steerable ablation catheter system having disposable shaft |
DE69730093T2 (de) | 1996-10-31 | 2006-07-20 | Takeda Pharmaceutical Co. Ltd. | Zubereitung mit verzögerter Freisetzung |
US6131570A (en) | 1998-06-30 | 2000-10-17 | Aradigm Corporation | Temperature controlling device for aerosol drug delivery |
KR20000057693A (ko) | 1996-12-20 | 2000-09-25 | 다케다 야쿠힌 고교 가부시키가이샤 | 지효성 제제의 제조 방법 |
US5891474A (en) | 1997-01-29 | 1999-04-06 | Poli Industria Chimica, S.P.A. | Time-specific controlled release dosage formulations and method of preparing same |
US5860957A (en) | 1997-02-07 | 1999-01-19 | Sarcos, Inc. | Multipathway electronically-controlled drug delivery system |
US6120751A (en) | 1997-03-21 | 2000-09-19 | Imarx Pharmaceutical Corp. | Charged lipids and uses for the same |
US6060082A (en) | 1997-04-18 | 2000-05-09 | Massachusetts Institute Of Technology | Polymerized liposomes targeted to M cells and useful for oral or mucosal drug delivery |
GB9711043D0 (en) | 1997-05-29 | 1997-07-23 | Ciba Geigy Ag | Organic compounds |
US5948433A (en) | 1997-08-21 | 1999-09-07 | Bertek, Inc. | Transdermal patch |
US6403597B1 (en) | 1997-10-28 | 2002-06-11 | Vivus, Inc. | Administration of phosphodiesterase inhibitors for the treatment of premature ejaculation |
US6037346A (en) | 1997-10-28 | 2000-03-14 | Vivus, Inc. | Local administration of phosphodiesterase inhibitors for the treatment of erectile dysfunction |
US6127363A (en) | 1997-10-28 | 2000-10-03 | Vivus, Inc. | Local administration of Type IV phosphodiesterase inhibitors for the treatment of erectile dysfunction |
EP0968711B9 (en) | 1997-10-28 | 2008-05-28 | Bando Chemical Industries, Ltd. | Dermatological patch sheet and process for producing base sheet therefor |
US6156753A (en) | 1997-10-28 | 2000-12-05 | Vivus, Inc. | Local administration of type III phosphodiesterase inhibitors for the treatment of erectile dysfunction |
US6548490B1 (en) | 1997-10-28 | 2003-04-15 | Vivus, Inc. | Transmucosal administration of phosphodiesterase inhibitors for the treatment of erectile dysfunction |
KR100577877B1 (ko) | 1998-01-16 | 2006-05-09 | 다케다 야쿠힌 고교 가부시키가이샤 | 서방성 조성물, 그것의 제조방법 및 용도 |
US6613358B2 (en) | 1998-03-18 | 2003-09-02 | Theodore W. Randolph | Sustained-release composition including amorphous polymer |
US6048736A (en) | 1998-04-29 | 2000-04-11 | Kosak; Kenneth M. | Cyclodextrin polymers for carrying and releasing drugs |
FR2778662B1 (fr) | 1998-05-12 | 2000-06-16 | Adir | Nouveaux composes cycliques substitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
KR19990085365A (ko) | 1998-05-16 | 1999-12-06 | 허영섭 | 지속적으로 약물 조절방출이 가능한 생분해성 고분자 미립구 및그 제조방법 |
US7238711B1 (en) | 1999-03-17 | 2007-07-03 | Cambridge University Technical Services Ltd. | Compounds and methods to inhibit or augment an inflammatory response |
US6248363B1 (en) | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
US6271359B1 (en) | 1999-04-14 | 2001-08-07 | Musc Foundation For Research Development | Tissue-specific and pathogen-specific toxic agents and ribozymes |
US6256533B1 (en) | 1999-06-09 | 2001-07-03 | The Procter & Gamble Company | Apparatus and method for using an intracutaneous microneedle array |
US7105571B2 (en) | 2000-01-10 | 2006-09-12 | Nexmed Holdings, Inc. | Prostaglandin compositions and methods of treatment for male erectile dysfunction |
US6323241B1 (en) | 2000-01-10 | 2001-11-27 | Nexmed (Holdings) Inc. | Prostaglandin compositions and methods of treatment for male erectile dysfunction |
US6693135B2 (en) | 2000-01-10 | 2004-02-17 | Nexmed (Holdings) Incorporated | Prostaglandin compositions and methods of treatment for male erectile dysfunction |
US6261595B1 (en) | 2000-02-29 | 2001-07-17 | Zars, Inc. | Transdermal drug patch with attached pocket for controlled heating device |
US6495154B1 (en) | 2000-11-21 | 2002-12-17 | Vivus Inc. | On demand administration of clomipramine and salts thereof to treat premature ejaculation |
JP2005503425A (ja) | 2001-05-24 | 2005-02-03 | アレックザ モレキュラー デリヴァリー コーポレイション | 所定の吸入ルートによる薬剤エステルの送出 |
PT2062914E (pt) | 2001-06-08 | 2014-07-18 | Ipsen Pharma Sas | Análogos quiméricos de somatostatina-dopamina |
EP1421955A1 (en) * | 2001-08-10 | 2004-05-26 | Hisamitsu Pharmaceutical Co., Inc. | Percutaneous absorption preparations |
DE10249401A1 (de) | 2002-10-23 | 2004-05-13 | Bernina Biosystems Gmbh | Liposomen formende Zusammensetzung |
WO2004091490A2 (en) | 2003-04-11 | 2004-10-28 | Societe De Conseils De Recherches Et D'applications Scientifiques S.A.S. | Somatostatin-dopamine chimeric analogs |
EP1663159A4 (en) | 2003-09-10 | 2010-06-09 | Map Pharmaceuticals Inc | AEROSOL FORMULATIONS FOR THE DELIVERY OF DIHYDROERGOTAMINE TO THE SYSTEMIC CIRCULATION BY PULMONARY INHALATION |
US7650848B2 (en) | 2004-02-17 | 2010-01-26 | University Of Florida Research Foundation, Inc. | Surface topographies for non-toxic bioadhesion control |
US9016221B2 (en) | 2004-02-17 | 2015-04-28 | University Of Florida Research Foundation, Inc. | Surface topographies for non-toxic bioadhesion control |
GB0511060D0 (en) | 2005-05-31 | 2005-07-06 | Novartis Ag | Organic compounds |
US8859579B2 (en) | 2008-03-21 | 2014-10-14 | Richard Andrew Sewell | Compostions and methods for preventing and/or treating disorders associated with cephalic pain |
US20100168119A1 (en) | 2008-11-05 | 2010-07-01 | Pharmorx, Inc. | Compositions and methods for minimizing or reducing agonist-induced desensitization |
WO2010065930A1 (en) | 2008-12-04 | 2010-06-10 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for treating or preventing narcotic withdrawal symptoms |
WO2011079313A1 (en) | 2009-12-23 | 2011-06-30 | Map Pharmaceuticals, Inc. | Novel ergoline analogs |
NZ604004A (en) | 2010-05-07 | 2014-06-27 | Gilead Connecticut Inc | Pyridone and aza-pyridone compounds and methods of use |
WO2012062676A1 (de) * | 2010-11-11 | 2012-05-18 | Sinoxa Pharma Ug | Lisurid, tergurid und derivate davon zur verwendung in der prophylaxe und/oder therapie fibrotischer veränderungen |
US8604035B2 (en) | 2011-06-23 | 2013-12-10 | Map Pharmaceuticals, Inc. | Fluoroergoline analogs |
WO2013095707A1 (en) * | 2011-12-19 | 2013-06-27 | Map Pharmaceuticals, Inc. | Novel iso-ergoline derivatives |
EP2793583A4 (en) * | 2011-12-21 | 2015-08-12 | Map Pharmaceuticals Inc | NOVEL NEUROMODULATORY CONNECTIONS |
US9012640B2 (en) | 2012-06-22 | 2015-04-21 | Map Pharmaceuticals, Inc. | Cabergoline derivatives |
US9670199B2 (en) | 2012-11-19 | 2017-06-06 | Regents Of The University Of Minnesota | Ergoline derivatives as dopamine receptor modulators |
US20140179705A1 (en) | 2012-12-21 | 2014-06-26 | Map Pharmaceuticals, Inc. | 8'-hydroxy-dihydroergotamine compounds and compositions |
JP2016503796A (ja) | 2012-12-21 | 2016-02-08 | マップ ファーマシューティカルズ インコーポレイテッド | フルオロエルゴリン誘導体およびその使用 |
EP2934529A1 (en) | 2012-12-21 | 2015-10-28 | MAP Pharmaceuticals, Inc. | Novel ergoline derivatives and uses thereof |
SG11201504931SA (en) | 2012-12-21 | 2015-07-30 | Map Pharmaceuticals Inc | Novel methysergide derivatives |
AU2013361337A1 (en) | 2012-12-21 | 2015-07-09 | Map Pharmaceuticals, Inc. | 8'-Hydroxy-Dihydroergotamine compounds and compositions |
WO2014186623A2 (en) | 2013-05-17 | 2014-11-20 | Biomed Valley Discoveries | Methods and compositions for the treatment of a chagas disease |
JP2018502889A (ja) | 2015-01-20 | 2018-02-01 | エックスオーシー ファーマシューティカルズ インコーポレイテッドXoc Pharmaceuticals, Inc | イソエルゴリン化合物およびその使用 |
CN107428745A (zh) | 2015-01-20 | 2017-12-01 | Xoc制药股份有限公司 | 麦角灵化合物及其用途 |
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- 2016-01-20 BR BR112017015510A patent/BR112017015510A2/pt not_active Application Discontinuation
- 2016-01-20 AU AU2016209490A patent/AU2016209490B2/en not_active Ceased
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AU2016209490B2 (en) | 2020-09-03 |
AU2016209490A1 (en) | 2017-08-31 |
EP3247357A4 (en) | 2018-07-11 |
US9676776B2 (en) | 2017-06-13 |
CN107405346A (zh) | 2017-11-28 |
MX2017009406A (es) | 2018-01-18 |
IL253459B (he) | 2020-10-29 |
US9815830B2 (en) | 2017-11-14 |
IL253459A0 (he) | 2017-09-28 |
US9777016B2 (en) | 2017-10-03 |
US20170233387A1 (en) | 2017-08-17 |
WO2016118539A2 (en) | 2016-07-28 |
US20160207920A1 (en) | 2016-07-21 |
US20170233404A1 (en) | 2017-08-17 |
BR112017015510A2 (pt) | 2018-01-30 |
CA2974113A1 (en) | 2016-07-28 |
EP3247357A2 (en) | 2017-11-29 |
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